Novel therapeutic approaches to correct retinal metabolic abnormalities in primary open-angle glaucoma and age-related macular degeneration

Common pathogenic aspects of age-related macular degeneration (AMD) and primary open-angle glaucoma (POAG), i.e., the role of free radicals inducing oxidative damage of the retina and optic nerve, are discussed. Factors that activate free radical reactions as well as multilevel antioxidant protection system are reviewed. Data derived from studies on current antioxidants that are used to treat and prevent dry AMD and glaucomatous optic nerve damage are compared. Neuroprotection for glaucoma will be considered soon as a basis for its treatment. B vitamins are generally included into therapeutic algorithms for glaucomatous optic neuropathy. While being metabolic therapeutics, they stimulate adaptive compensatory mechanisms and reduce the severity of various pathological processes, e.g., hypoxia, lipid peroxidation etc. Neurotrophic, antioxidant, and regenerative effects of B vitamins as wells as their involvement in metabolism, myelin
synthesis and other processes are of special importance for ophthalmologists. Currently, several vitamin and mineral supplements that differ in composition, dosage, and schedule are approved in Russia. SuperOptic, a biologically active
additive, contains more free lutein (10 mg) and zeaxanthin (500 μg) as well as potent antioxidants (vitamin E and vitamin C), microelements (zinc and copper), and balanced vitamin B complex. These components play an important role in ocular health. SuperOptic can be recommended for the prevention and treatment of AMD and glaucomatous optic nerve damage.

1. Kugoyeva E. E., Podgornaya N. N., Sherstneva L. V., Petrov S. Y., Cherkashina A. V. [Evaluation of eye hemodinamics and somatic status in patients with primary openangle glaucoma]. Izuchenie gemodinamiki glaza i obshhesomaticheskogo statusa bol’nyh s pervichnoj otkrytougol’noj glaukomoj. [Annals of ophthalmology]. Vestnik Oftalmology 2000; 4: 26‑28. (in Russ.).

2. Shmyreva V. F., Petrov S. Ju., Makarova A. S. [Causes of long-term efficacy decrease of antiglaukoma interventions and possibilities of its improvement]. Prichiny snizhenija otdalennoj gipotenzivnoj jeffektivnosti antiglaukomatoznyh operacij i vozmozhnosti ee povyshenija. [Glaucoma]. Glaukoma. 2010; 126 (2): 43‑49. (in Russ.).

3. Kurysheva N. I. [Optical neuropathy in patients with glaucoma]. Glaukomnaja opticheskaja nejropatija. Moscow. 2006. 135p. (in Russ.).

4. Bressler N. M., Silva J. C., Bressler S. B. et al. Clinicopathologic correlation of drusen and retinal pigment epithelial abnormalities in age-related macular degeneration. Retina 2005; 25: 130‑42.

5. Hyun H. J., Sohn J. H., Ha D. W. et al. Depletion of intracellular zinc and cooper with TPEN results in apoptosis of cultured human retinal pigment epithelial cells// Invest. Ophthalmol. Vis. Sci. 2001; 42 (2): 460‑465.

6. Klein R., Klein B. E., Jensen S. C. et al. Medication use and the 5‑year incidence of early age-related maculopathy: the Beaver Dam Eye Study. Arch. Ophthalmol. 2001;119 (9):1354‑9.

7. Ostrovskij M. A. [Clinical physiology of vision]. Klinicheskaja fiziologija zrenija. Moscow, 2002. 39 pp. (in Russ.).

8. The Age- Related Eye Disease Study Research Group. A randomized, placebo- controlled, clinical trial of high-dose supplementation with vitamins C and E, beta-carotene, and zinc for age-related macular degeneration and vision loss. AREDS Report No.8. Arch. Ophthalmol. 2001;119: 1417‑1436.

9. Beatty S., Koh H-H. Henson D., Bouston M. et al. Role of oxidative stress in the pathogenesis of age-related macular degeneration. Surv. Ophthalmol. 2000; 45:115‑134.

10. Gottsch J. D, Bynoe L. A., Harlan J. B. et al. Light-induced deposits in Bruch’s membrane of protoporphyric mice. Arch. Ophthalmol. 1993;111:126‑129.

11. Norkus E. P., Norkus K. L., Dharmarajan T. S. et al. Serum lutein response is greater from free lutein than from esterified lutein during 4 weeks of supplementation in healthy adults. Am Coll Nutr. 2010;29:575‑85.

12. Vinderling J. R., Dielemans I., Bots M. L. Age-related macular degeneration is associated with atheroclerosis. The Rotterdam Study. Am. J. Opid. 1995;142 (4):404‑409.

13. Delcourt C, Carriere I, Delage M, et al, POLA Study Group. Plasma lutein and zeaxanthin and other carotenoids as modifiable risk factors for age — related maculopathy and cataract: the POLA Study. Invest Ophthalmol Vis Sci. 2006; 47:2329‑2335.

14. Kiseleva T. N., Polunin G. S., Budzinskaja M. V., Lagutina Ju. M., Vorob’eva M. V. [Modern approaches to treatment and prevention of macular degeneration]. Sovremennye podhody k lecheniju i profilaktike vozrastnoj makuljarnoj degeneracii. [Russian Medical Journal]. Russkij medicinskij zhurnal 2007; 2:78‑79. (in Russ.).

15. Wang X., Yin W., Dong X. et al. Experimental high IOP model and hypertension-induced lipid hyperoxygen reaction. Chinese-Ophthalmic-Res. 2004; 22:620‑622.

16. Zeimer M., Hense H. W., Heimes B. et al. The macular pigment: short– and intermediate — term changes of macular pigment optical density following supplementation with lutein and zeaxanthin and co — antioxidants. The LUNA Study / Ophthalmologe. 2009; 106:29‑36.

17. Smirnoff N. Ascorbic acid: metabolism and functions of a multi-facetted molecule. Current Opinion in Plant Biology 2000;3: 229‑235.

18. Moeller S. M., Parekh N., Tinker L. et al. Associations between intermediate age — related macular degeneration and lutein and zeaxanthin in the Carotenoids in Age — related Eye Disease Study (CAREDS): ancillary study of the Women’s Health Initiative. Arch Ophthalmol. 2006; 124:1151‑1162.

19. Beatty S., Koh H-H. Henson D., Bouston M. et al. Role of oxidative stress in the pathogenesis of age-related macular degenerationю Surv. Ophthalmol. 2000; 45:115‑134.

20. Bone R. A., Landrum J. T., Mayne S. T. et al. Macular pigment in donor eyes with and without AMD: a case-control study. Invest. Ophthalmol. Vis. Sci. 2001; 42: 235‑240.

21. Delcourt C, Carriere I, Delage M, et al, POLA Study Group. Plasma lutein and zeaxanthin and other carotenoids as modifiable risk factors for age — related maculopathy and cataract: the POLA Study. Invest Ophthalmol Vis Sci 2006; 47:2329‑2335.

22. Seddon J. M., Ajani U. A., Sperduto R. D. Dietary carotenoids, vitamin A, C and E and advanced age-related macular degeneration: Eye Disease case-Control Study Group. JAVA 1994; 272: 1413‑1420.

23. Richer S., Stiles W., Statkute L. et al. Double-masked, placebo-controlled, randomized trial of lutein and antioxidant supplementation in the intervention of atrophic age-related macular degeneration: the Veterans LAST study (Lutein Antioxidant Supplementation Trial). Optometry 2004; 75 (4): 216‑30.

24. Tan J. S., Wang J. J., Flood V., et al. Dietary antioxidants and the long — term incidence of age — related macular degeneration: the Blue Mountains Eye Study.Ophthalmology. 2008; 115:334‑341.

25. Zeimer M., Hense H. W., Heimes B. et al. The macular pigment: short– and intermediate — term changes of macular pigment optical density following supplementation with lutein and zeaxanthin and co — antioxidants. The LUNA Study / Ophthalmologe. 2009; 106:29‑36.

26. SanGiovanni J. P., Agron E., Clemons T. E. et al. Omega-3 long-chain polyunsaturated fatty acid intake inversely associated with 12‑year progression to advanced age-related macular degeneration. Arch Ophthalmol. 2009; 127 (1): 110‑112.

27. SanGiovanni J. P., Chew E. Y., Agron E. et al. The relationship of dietary omega-3 longchain polyunsaturated fatty acid intake with incident age-related macular degeneration: AREDS report no. 23. Arch Ophthalmol. 2008; 126 (9): 1274‑1279.

28. Lutein + zeaxanthin and omega-3 fatty acids for age-related macular degeneration: the Age-Related Eye Disease Study 2 (AREDS2) randomized clinical trial. JAMA 2013;19: 2005‑2015.

29. Yamamoto T. The dawn of neuroprotective therapy for glaucoma optic neuropathy. Nippon Ganka Zasshi. 2001;105:866‑883.